Treatment Trends and Clinical Outcomes of Left-Sided RAS/RAF Wild-Type Metastatic Colorectal Cancer in the United States

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Christopher Nevala-Plagemann Division of Medical Oncology, Huntsman Cancer Institute at the University of Utah; and

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Siddharth Iyengar Department of Internal Medicine, and

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Andrew D. Trunk Department of Internal Medicine, and

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Lisa Pappas Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.

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Benjamin Haaland Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.

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Ignacio Garrido-Laguna Division of Medical Oncology, Huntsman Cancer Institute at the University of Utah; and

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Background: Post hoc analysis of the CALGB/SWOG 80405 trial suggests that anti-EGFR therapy may be superior to bevacizumab when added to first-line chemotherapy in patients with metastatic colorectal cancer (mCRC) who have left-sided primary tumors. We evaluated trends in use of anti-EGFR agents in patients with left-sided RAS/RAF wild-type (WT) mCRC and compared clinical outcomes among the most commonly used treatment strategies. Methods: A nationwide electronic health record (EHR)–derived deidentified database was reviewed for patients with left-sided RAS/RAF WT mCRC. Treatment trends over time were assessed by fitting a linear model to the percentage of patients receiving anti-EGFR therapy. A propensity score weighted Cox model was used to compare overall survival (OS) stratified by first-line targeted therapy received. Results: A total of 1,607 patients with left-sided RAS/RAF WT mCRC received standard first-line chemotherapy. Of these, 965 (60%) received bevacizumab and 186 (12%) received an anti-EGFR agent. The percentage of patients receiving an anti-EGFR increased from 9% in 2013 to 16% in 2018. Median OS for patients treated with chemotherapy alone was 27.3 months (95% CI, 24.8–32.3), 27.5 months with bevacizumab (95% CI, 25.8–28.9; hazard ratio [HR], 0.88; P=.33), and 42.9 months with an anti-EGFR agent (95% CI, 36.0 to not reached; HR, 0.52; P=.005). Conclusions: This analysis suggests that chemotherapy with bevacizumab remained the most widely used first-line treatment strategy for patients with left-sided RAS/RAF WT mCRC in the United States in 2018. Despite this preference, treatment with an anti-EGFR agent was associated with improved OS.

Submitted March 26, 2021; final revision received June 29, 2021; accepted for publication July 1, 2021. Published online February 4, 2022.

Author contributions: Study concept and design: All authors. Administrative support: Nevala-Plagemann, Garrido-Laguna. Provision of study materials or patients: Nevala-Plagemann. Data acquisition: Nevala-Plagemann, Pappas, Haaland. Data analysis and interpretation: All authors. Manuscript preparation: All authors.

Disclosures: Dr. Haaland has disclosed receiving travel funds from Flatiron Health. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this publication was supported by the NCI of the NIH under award number P30CA042014-23.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Correspondence: Ignacio Garrido-Laguna, MD, PhD, Division of Medical Oncology, Huntsman Cancer Institute, 2000 Circle of Hope, Suite 5507, Salt Lake City, UT 84112. Email: Ignacio.Garrido-Laguna@hci.utah.edu
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